Substrate-induced phenotypic switches of human smooth muscle cells: an in vitro study of in-stent restenosis activation pathways.

Guildford, Anna L, Stewart, Helen J S, Morris, Christopher and Santin, Matteo (2011) Substrate-induced phenotypic switches of human smooth muscle cells: an in vitro study of in-stent restenosis activation pathways. Journal of the Royal Society Interface, 8 (58). pp. 641-9. ISSN 1742-5689

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Abstract

In-stent restenosis is a clinical complication following coronary angioplasty caused by the implantation of the metal device in the atherosclerotic vessel. Histological examination has shown a clear contribution of both inflammatory and smooth muscle cells (SMCs) to the deposition of an excess of neointimal tissue. However, the sequence of events leading to clinically relevant restenosis is unknown. This paper aims to study the phenotype of SMCs when adhering on substrates and exposed to biochemical stimuli typical of the early phases of stent implantation. In particular, human SMC phenotype was studied when adhering on extracellular matrix-like material (collagen-rich gel), thrombus-like material (fibrin gel) and stent material (stainless steel) in the presence or absence of a platelet-derived growth factor (PDGF) stimulus. Cells on the collagen and fibrin-rich substrates maintained their contractile phenotype. By contrast, cells on stainless steel acquired a secretory phenotype with a proliferation rate 50 per cent higher than cells on the natural substrates. Cells on stainless steel also showed an increase in PDGF-BB receptor expression, thus explaining the increase in proliferation observed when cells were subject to PDGF-BB stimuli. The stainless steel substrate also promoted a different pattern of β1-integrin localization and an altered expression of hyaluronan (HA) synthase isoforms where the synthesis of high-molecular-weight HA seemed to be favoured. These findings highlighted the induction of a phenotypic pattern in SMC by the stainless steel substrate whereby the formation of a HA-rich neointimal tissue is enhanced.

Item Type: Article
Keywords: ain stent restenosis, smooth muscle
Schools and Departments: Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: Q Science > QH Natural history > QH0301 Biology
Depositing User: Helen Stewart
Date Deposited: 18 Aug 2011 13:30
Last Modified: 01 Sep 2017 10:14
URI: http://sro.sussex.ac.uk/id/eprint/7041
Google Scholar:0 Citations
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